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Chemistry

Disease Correlation

The results of carbohydrate tests paint a picture of the patient’s metabolic health. Certain patterns of results point to specific disease states, and understanding these correlations is key

Diabetes Mellitus (DM)

  • Definition: A group of metabolic disorders characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both
  • Types
    • Type 1 Diabetes (T1DM): Autoimmune destruction of pancreatic beta cells, leading to absolute insulin deficiency
    • Type 2 Diabetes (T2DM): Progressive insulin resistance and relative insulin deficiency
    • Gestational Diabetes (GDM): Diabetes diagnosed during pregnancy
    • Other specific types of diabetes: Due to genetic defects, medications, or other conditions
  • Laboratory Findings
    • Fasting Plasma Glucose (FPG): ≥ 126 mg/dL (7.0 mmol/L) on more than one occasion
    • Oral Glucose Tolerance Test (OGTT): 2-hour plasma glucose ≥ 200 mg/dL (11.1 mmol/L)
    • HbA1c: ≥ 6.5%
    • Random Plasma Glucose: ≥ 200 mg/dL (11.1 mmol/L) in a patient with classic symptoms of hyperglycemia (polyuria, polydipsia, unexplained weight loss)
    • Urine Glucose: Positive (in cases of significant hyperglycemia)
    • Ketones: Positive (especially in T1DM with uncontrolled hyperglycemia)
  • Disease State Correlation
    • Elevated FPG, OGTT, and HbA1c levels are diagnostic of diabetes mellitus
    • The severity of hyperglycemia correlates with the risk of developing long-term complications (e.g., retinopathy, nephropathy, neuropathy, cardiovascular disease)
    • Presence of ketones indicates uncontrolled diabetes and increased risk of diabetic ketoacidosis (DKA)
  • Clinical Significance
    • Early diagnosis and management of diabetes are essential to prevent or delay the onset of complications
    • Monitoring of glucose levels and HbA1c is crucial for assessing treatment effectiveness and adjusting therapy as needed
    • Patient education and lifestyle modifications (diet, exercise) are important components of diabetes management

Prediabetes

  • Definition: A state of impaired glucose regulation characterized by either impaired fasting glucose (IFG) or impaired glucose tolerance (IGT)
  • Laboratory Findings
    • Impaired Fasting Glucose (IFG): FPG 100-125 mg/dL (5.6-6.9 mmol/L)
    • Impaired Glucose Tolerance (IGT): 2-hour plasma glucose during OGTT 140-199 mg/dL (7.8-11.0 mmol/L)
    • HbA1c: 5.7-6.4%
  • Disease State Correlation
    • Prediabetes indicates an increased risk of developing type 2 diabetes, cardiovascular disease, and other complications
    • The higher the glucose levels, the greater the risk of progression to diabetes
  • Clinical Significance
    • Early identification of prediabetes allows for intervention with lifestyle modifications (diet, exercise) to prevent or delay the onset of type 2 diabetes
    • Regular monitoring of glucose levels and HbA1c is recommended

Gestational Diabetes Mellitus (GDM)

  • Definition: Diabetes diagnosed during pregnancy
  • Screening
    • Typically performed between 24-28 weeks of gestation
    • 1-hour Glucose Challenge Test (GCT): 50-gram glucose load, measure plasma glucose after 1 hour. A value ≥ 130-140 mg/dL (7.2-7.8 mmol/L) is considered positive and requires a follow-up OGTT
  • Diagnosis
    • Oral Glucose Tolerance Test (OGTT) with a 75-gram or 100-gram glucose load
    • Diagnostic criteria vary depending on the organization (e.g., ADA, WHO, IADPSG)
    • Common criteria (Carpenter-Coustan, 100-gram OGTT):
      • Fasting ≥ 95 mg/dL (5.3 mmol/L)
      • 1-hour ≥ 180 mg/dL (10.0 mmol/L)
      • 2-hour ≥ 155 mg/dL (8.6 mmol/L)
      • 3-hour ≥ 140 mg/dL (7.8 mmol/L)
      • Two or more values meeting or exceeding these criteria establish the diagnosis
  • Laboratory Findings
    • Elevated glucose levels during OGTT
  • Disease State Correlation
    • GDM is associated with increased risks for both the mother and the fetus, including macrosomia (large baby), hypoglycemia, preeclampsia, and increased risk of developing type 2 diabetes later in life
  • Clinical Significance
    • Early diagnosis and management of GDM are essential to reduce the risks for both the mother and the fetus
    • Management typically involves dietary modifications, exercise, and sometimes insulin therapy
    • Postpartum glucose testing is recommended to assess for persistent diabetes

Hypoglycemia

  • Definition: Abnormally low blood glucose levels
  • Causes
    • Excess insulin administration in patients with diabetes
    • Oral hypoglycemic agents
    • Missed meals or inadequate carbohydrate intake
    • Excessive exercise
    • Alcohol consumption
    • Certain medical conditions (e.g., liver disease, kidney disease, hormone deficiencies, insulinoma)
  • Laboratory Findings
    • Plasma glucose < 70 mg/dL (3.9 mmol/L)
    • In severe cases, glucose may be < 50 mg/dL (2.8 mmol/L)
  • Disease State Correlation
    • Symptoms of hypoglycemia include sweating, shakiness, anxiety, palpitations, confusion, dizziness, blurred vision, difficulty speaking, seizures, loss of consciousness
    • Severe hypoglycemia can lead to brain damage and death
  • Clinical Significance
    • Prompt recognition and treatment of hypoglycemia are essential
    • Treatment typically involves ingestion of fast-acting carbohydrates (e.g., glucose tablets, juice)
    • Underlying causes of hypoglycemia should be identified and addressed

Diabetic Ketoacidosis (DKA)

  • Definition: A life-threatening complication of diabetes characterized by hyperglycemia, ketosis, and metabolic acidosis
  • Etiology
    • Primarily occurs in patients with type 1 diabetes due to absolute insulin deficiency
    • Can also occur in patients with type 2 diabetes under conditions of severe stress, infection, or illness
  • Laboratory Findings
    • Plasma Glucose: Elevated, typically > 250 mg/dL (13.9 mmol/L)
    • Ketones: Elevated in serum or urine
      • Beta-hydroxybutyrate is the predominant ketone body
    • Arterial Blood Gases (ABG)
      • pH < 7.3
      • Bicarbonate (HCO3-) < 15 mEq/L
    • Electrolytes
      • Anion gap > 12 mEq/L
      • Potassium may be normal, elevated, or decreased
  • Disease State Correlation
    • DKA is a medical emergency requiring prompt treatment
    • Symptoms include polyuria, polydipsia, nausea, vomiting, abdominal pain, weakness, fruity-smelling breath, and altered mental status
  • Clinical Significance
    • Prompt diagnosis and treatment of DKA are essential to prevent complications such as cerebral edema, cardiac arrhythmias, and death
    • Treatment involves insulin therapy, fluid resuscitation, and electrolyte replacement

Hyperosmolar Hyperglycemic State (HHS)

  • Definition: A life-threatening complication of diabetes characterized by severe hyperglycemia, hyperosmolarity, and dehydration, without significant ketosis
  • Etiology
    • Primarily occurs in patients with type 2 diabetes
    • Often precipitated by illness, infection, or dehydration
  • Laboratory Findings
    • Plasma Glucose: Very elevated, typically > 600 mg/dL (33.3 mmol/L)
    • Serum Osmolality: > 320 mOsm/kg
    • Ketones: Absent or mild
    • Arterial Blood Gases (ABG): pH > 7.3, bicarbonate > 15 mEq/L
    • Electrolytes: May show electrolyte imbalances
  • Disease State Correlation
    • HHS is a medical emergency requiring prompt treatment
    • Symptoms include severe dehydration, altered mental status, seizures, and coma
  • Clinical Significance
    • Prompt diagnosis and treatment of HHS are essential to prevent complications such as cerebral edema, thromboembolic events, and death
    • Treatment involves fluid resuscitation, insulin therapy, and electrolyte replacement

Galactosemia

  • Definition: A rare genetic metabolic disorder characterized by the inability to metabolize galactose due to a deficiency in one of the enzymes involved in galactose metabolism
  • Types
    • Classic Galactosemia: Deficiency of galactose-1-phosphate uridyltransferase (GALT)
    • Galactokinase Deficiency: Deficiency of galactokinase (GALK)
    • UDP-Galactose-4-Epimerase Deficiency: Deficiency of UDP-galactose-4-epimerase (GALE)
  • Laboratory Findings
    • Elevated galactose levels in blood and urine
    • Deficiency of the specific enzyme in red blood cells
    • Urine reducing substances positive (non-glucose)
  • Disease State Correlation
    • Symptoms of galactosemia include feeding difficulties, vomiting, diarrhea, lethargy, jaundice, hepatomegaly, cataracts, and intellectual disability
    • Early diagnosis and treatment are essential to prevent long-term complications
  • Clinical Significance
    • Newborn screening for galactosemia is performed in many countries
    • Treatment involves strict dietary restriction of galactose

Hereditary Fructose Intolerance (HFI)

  • Definition: A rare genetic metabolic disorder caused by a deficiency in aldolase B, leading to the accumulation of fructose-1-phosphate in the liver, kidney, and small intestine
  • Laboratory Findings
    • Hypoglycemia after fructose ingestion
    • Elevated liver enzymes (AST, ALT)
    • Elevated bilirubin
    • Prolonged prothrombin time (PT)
    • Urine reducing substances positive (non-glucose)
    • Genetic testing confirms the diagnosis
  • Disease State Correlation
    • Symptoms of HFI include vomiting, abdominal pain, hypoglycemia, liver damage, and kidney dysfunction
    • Repeated fructose ingestion can lead to liver failure and death
  • Clinical Significance
    • Early diagnosis and treatment are essential to prevent long-term complications
    • Treatment involves strict dietary restriction of fructose, sucrose, and sorbitol

Key Terms

  • Diabetes Mellitus: A group of metabolic disorders characterized by hyperglycemia
  • Prediabetes: A state of impaired glucose regulation
  • Gestational Diabetes: Diabetes diagnosed during pregnancy
  • Hypoglycemia: Abnormally low blood glucose levels
  • Diabetic Ketoacidosis (DKA): A life-threatening complication of diabetes characterized by hyperglycemia, ketosis, and metabolic acidosis
  • Hyperosmolar Hyperglycemic State (HHS): A life-threatening complication of diabetes characterized by severe hyperglycemia, hyperosmolarity, and dehydration without significant ketosis
  • Galactosemia: A genetic disorder characterized by the inability to metabolize galactose
  • Hereditary Fructose Intolerance (HFI): A genetic disorder caused by a deficiency in aldolase B, leading to the accumulation of fructose-1-phosphate
  • Fasting Plasma Glucose (FPG): Glucose level after an overnight fast
  • Oral Glucose Tolerance Test (OGTT): A test to assess glucose metabolism
  • HbA1c: A measure of average glucose levels over 2-3 months
  • Ketones: Products of fat breakdown